恶性血液病患者血清红细胞生成素、血小板生成素变化及其临床意义

采用夹心酶联免疫法测定40例恶性血液病患者（观察组）及18例健康人（对照组）血清红细胞生成素（EPO）、血小板生成素（TPO）、血红蛋白（Hb）、红细胞（RBC）及血小板（PLT）水平。结果观察组血清EPO水平明显高于对照组（P〈0．05），且与Hb及RBC计数呈负相关（P均〈0．05）；血清TPO水平白血病患者（20例）均显著高于对照组，其他恶性血液病患者（20例）则低于对照组，除慢性白血病患者血清TPO水平与PLT计数不相关外，其他恶性血液病患者均与PLT计数呈负相关。提示除白血病外，其他恶性血液病患者伴发的贫血均可应用重组人促红细胞生成素（rhEPO）治疗，伴PLT减少时，应用重组人促血小板生成亲（rhTPO）治疗有益。     

ITP患者血清血小板生成素水平与临床治疗效果的关系

目的 探讨血小板生成素（TPO）对特发性血小板减少性紫癜（ITP）临床治疗效果的影响。方法 将25例初治ITP患者按治疗效果分为有效组和无效组,另设正常对照组22例。采用ELISA法和放免法分别检测治疗前后血清TPO水平,取治疗前骨髓涂片计数巨核细胞数量。结果 无效组TPO水平明显高于有效者及对照组（P均〈0．05）,有效者与对照组间无显著性差异;无效者巨核细胞计数则显著低于有效者（P〈0．01）。结论 血清高水平TPO可能预示ITP治疗困难;TPO治疗有效与无效者的发病机理可能存在差异。     

慢性肝炎

慢性肝病血小板生成减少的机制探讨——叶军等（江苏泰州市人民医院检验科225300）；《海南医学》，2006，17（2）：126．127【目的：探讨慢性肝病血小板生成减少的机制。方法：ELISA双抗夹心法测定正常人群及慢性肝病患者的血小板生成素水平（Tpo）水平。结果：（1）肝病患者Tpo〉143组与Tpo〉143组总胆固醇（CHOL）水平比较有显著性差异（P〈0．05）；其他生化指标无显著性差异。（2）肝病患者血小板正常组（38例）与减少组（37例）Tpo水平比较有显著性差异，[044．76&;#177;108．93）vs（100．19&;#177;66．43）pg／ml。P〈0．05]。但Tpo水平与血小板计数不相关，（r印．175，P〉0．05）。结论：慢性肝病患者肝脏的合成功能下降导致Tpo水平的降低，而Tpo水平降低是血小板减少的一个重要原因。】     

网织血小板在血小板减少性疾病中的临床意义

网织血小板；血小板减少症特发性血小板减少性紫癜（rrP）是因免疫机制使血小板破坏增多的临床综合征。血小板减少原因归为两类：血小板生成减少和血小板消耗或破坏过多。网织血小板（RP）是新近从骨髓中释放入外周血中的血小板，RP数目反映了人体血小板的更新速度、血小板生成能力。2002年11月-2004年6月我们检测50例健康人、48例ITP病人和其中30例获完全缓解ITP及35例急性白血病（AL）、25例慢性再生障碍性贫血（CAA）外周血的RP％和绝对计数，旨在初步探讨RP在血小板减少性疾病中的临床意义。     

血小板减少症患者检测血清幽门螺杆菌抗体的临床研究

目的：探讨临床上血小板减少的致病原因，了解幽门螺杆菌（Hp）感染在血小板减少症患者中的发病情况。方法：对320例血小板减少症患者定期检测血小板、血小板抗体、血清Hp抗体，部分患者检测胃液Hp抗体、血小板生成索（Tpo）水平；对Hp阳性患者给予抗Hp治疗，并观察血小板的变化。结果：31例患者存在Hp抗体阳性，感染率为9．7％，其Tpo水平与正常对照差异无统计学意义（P〉0．05）。给予抗Hp治疗后，血小板明显上升。结论：Hp感染是血小板减少症的重要致病原因，根治Hp感染是治疗血小板减少症的手段之一。     

溃疡性结肠炎患者血小板计数及凝血功能检测的临床意义

目的探讨检测溃疡性结肠炎患者血小板计数和凝血功能的临床意义。方法检测68例溃疡性结肠炎患者及26例对照组血小板计数及凝血功能,分析两者对患者临床病情程度的影响及其相关性。结果活动期溃疡性结肠炎患者血小板计数及纤维蛋白原明显高于缓解期患者和对照组（P〈0．05）,凝血酶原时间明显低于缓解期患者和对照组（P〈0．05）。重度溃疡性结肠炎患者血小板计数及纤维蛋白原明显高于中、轻度患者（P〈0．05）,凝血酶原时间明显低于中、轻度溃疡性结肠炎患者（P〈0．05）。溃疡性结肠炎患者血小板计数与凝血酶原时间变化存负相关,与纤维蛋白原存在正相关。结论血小板计数及凝血功能检测对判断溃疡性结肠炎活动性及其严重程度具有重要临床价值。     

122例单采血小板输注的临床观察

目的：对122例血小板减少症患者输注1单位单采血小板效果的实验室观察。方法：按血小板输血史将患者分为3组，A组（首次输血者，41例）；B组（重复输血者，69例）；C组（频繁输血者，12例）。血小板输注1h和24h后，比较患者校正血小板计数增加值（CCI）和血小板回收率（PPR）。结果：A组、B组、C组间CCI、PPR差异有统计学意义（P〈0．05）；血小板减少症组血小板输注无效率低于血液病组。结论：单采血小板输注是临床控制出血重要方法，尤其对首次输血者及一般重复输血者（2～10次）有效，可起到更好的预防及治疗效果；频繁输血者（≥11次）输注血小板后疗效较低，可能与患者输血前血小板基数较低及频繁输血导致血小板输注无效有关，未来的研究需要收集患者临床资料以更好地把握此类患者血小板输注效果。     

以血小板显著增高为特点的慢性粒细胞白血病三例

例1，女，29岁。2006年6月体检时发现血小板增高，血常规：白细胞计数6．88×10^9／L，血红蛋白110g/L，血小板计数4080×10^9／L。于2006年7月查骨髓示骨髓增生明显活跃，巨核细胞异常增生，考虑原发性血小板增多症，患者未行治疗。     

网织血小板对急性非淋巴细胞性白血病化疗患者骨髓功能恢复的评价作用

目的 探讨急性非淋巴细胞性白血病（ANLL）化疗过程中外周血网织血小板（RP）判断骨髓造血功能早期恢复的临床价值。方法 应用流式细胞仪、血细胞计数仪检测25例ANLL患者（ANLL组）化疗前、骨储抑制期、骨髓恢复期及化疗后血小板计数（PLT）、网织血小板绝对值（RP）、网织血小板百分数（RP％），并与30例健康人（对照组）进行比较。结果 ANLL组化疗前PLT、RP低于对照组，P均〈0．05；RP％与对照组比较，P〉0．05；骨髓恢复期RP、RP％高于骨髓抑制期及化疗后（P均〈0．05），而PLT计数无显著改变（P〉0．05），ANLL患者RPoA与PLT呈负相关（r=-0．373，P〈0．05）。结论 与PLT比较，RP能更好的反映ANLL患者的骨硼恢复功能．并可指导临床治疗。     

慢性乙型肝炎肝硬化血小板减少影响因素的研究进展

综述慢性乙型肝炎肝硬化血小板减少患者的血小板相关指标、肝纤维化指标、血小板生成素等各项指标的研究及各指标间的相互联系,以了解其研究进展,以便更深层次的探讨慢性乙肝肝硬化的发病机制。血小板减少的原因是由于脾功能亢进引起,还是由于TPO水平降低,或是乙型肝炎病毒侵犯骨髓影响巨核细胞,或是血小板本身的质的变化引起均有待于更系统、更全面的研究。     

病毒性肝炎血小板减少症影响因素的研究

目的探讨病毒性肝炎血小板减少症的发病机制.方法 84例病毒性肝炎患者和20名健康志愿者分为3组,A组(48例病毒性肝炎并血小板减少症患者)、B组(36例病毒性肝炎血小板正常患者)和C组(20名健康志愿者),分别采用酶联免疫吸附法、流式细胞术、腹部彩色B超检测3组血清血小板生成素(TPO)水平、血小板相关免疫球蛋白(PAIg)及其类别PAIgG、PAIgA、PAIgM水平、脾脏大小,采用骨髓穿刺术对其中74例行骨髓细胞学检查.结果血清TPO水平A组低于C组(P<0.01)和B组(P<0.05),严重肝病血清TPO水平与血小板数相关(r=0.374,P<00.01).PAIg、PAIgG水平A组明显高于B组(P<0.001)和C组(P<0.01),血小板数与PAIg水平呈负相关(r=0.446,P<0.01),血小板数与PAIgG水平亦呈负相关(r=-0.462,P<0.01).脾脏肿大发生率A组(77.1%)明显高于B组(47.2%,P<0.01),C组无脾脏肿大发生,血小板数与脾脏大小呈负相关(r=-0.5 81,P<0.01).74例骨髓象显示A组有4例呈骨髓抑制象改变,B组和C组无一例有上述改变.结论严重肝功能受损时血清TPO水平下降,与血小板数减少直接相关.PAIg介导的自身免疫机制在病毒性肝炎血小板减少症中可能起重要作用.脾脏肿大是引起病毒性肝炎血小板减少的因素.初步发现慢性肝病有骨髓抑制现象,可能成为引起病毒性肝炎血小板减少的因素之一.     

Thrombocytopenia associated with liver cirrhosis and hepatitis C viral infection: role of thrombopoietin

BACKGROUND/AIMS: Thrombocytopenia in chronic liver diseases has traditionally been considered a consequence of platelet pooling and destruction in spleen. We tried to evaluate the influence of thrombopoietin, the physiological regulator of thrombopoiesis, on the origin of this thrombocytopenia. METHODOLOGY: We determined serum thrombopoietin levels by ELISA in thrombocytopenic patients with liver cirrhosis (n = 32) and with chronic hepatitis C viral infection (n = 23). A group of 43 healthy subjects was used as a control. RESULTS: Liver cirrhosis patients presented slightly, but not significantly, lower serum thrombopoietin levels (104 +/- 56 pg/mL) than controls (121 +/- 58 pg/mL) or patients infected with chronic hepatitis C virus (125 +/- 40 pg/mL). No correlations were found between serum thrombopoietin concentrations and liver tests or hematological parameters. CONCLUSIONS: We conclude that low thrombopoietin production may play a role, along with hypersplenism, in the development of thrombocytopenia in patients with liver cirrhosis. Normal thrombopoietin levels exclude a defect in thrombopoietin production as a possible etiology for the thrombocytopenia in patients with chronic hepatitis C viral infection. However, a direct viral megakaryocyte infection or an immune mechanism could explain this thrombocytopenia, according to the thrombopoietin levels detected.     

Three parameters, plasma thrombopoietin levels, plasma glycocalicin levels and megakaryocyte culture, distinguish between different causes of congenital thrombocytopenia

Fourteen children with congenital thrombocytopenia were analysed in order to unravel the mechanisms underlying their thrombocytopenia and to evaluate the value of new laboratory tests, namely measurement of plasma thrombopoietin (Tpo) and glycocalicin (GC) levels and analysis of megakaryocytopoiesis in vitro. Three groups of patients were included. The first group (n = 6) was diagnosed with congenital amegakaryocytic thrombocytopenia. They had no megakaryocytes in the bone marrow, three out of four patients showed no megakaryocyte formation in vitro, and all had high Tpo and low GC levels. Mutations in the thrombopoietin receptor gene, c-mpl, were the cause. The second group of patients (n = 3) had normal Tpo and severely decreased GC levels. In bone marrow, normal to increased numbers of atypical, dysmature megakaryocytes were present. In vitro megakaryocyte formation was quantitatively normal. A defect in final megakaryocyte maturation and subsequent (pro-)platelets may be the cause of the thrombocytopenia. The patients in the third group (n = 5) had Wiskott-Aldrich syndrome (WAS). They had normal Tpo and GC levels and normal megakaryocyte formation both in vivo and in vitro. This corresponded with the generally accepted hypothesis that thrombocytopenia in WAS is due to increased platelet turnover. In conclusion, different causes of congenital thrombocytopenia can be distinguished using three parameters: Tpo and GC plasma levels and in vitro analysis of megakaryocytopoiesis. Therefore, these parameters may be helpful in early diagnosis of different forms of congenital thrombocytopenia.     

Hepatic fibrosis plays a central role in the pathogenesis of thrombocytopenia in patients with chronic viral hepatitis

The pathogenesis of thrombocytopenia in chronic hepatitis is not well known. This study evaluated the relationship between liver injury, serum thrombopoietin, splenomegaly and thrombocytopenia in chronic viral hepatitis. Two hundred and nine patients were enrolled, 85 with splenomegaly and 124 without. Thrombocytopenia was present in 71% and 23% of patients with or without splenomegaly respectively. In subjects with low platelet count, those with splenomegaly showed significantly lower platelet numbers than those without splenomegaly. The spleen size correlated with portal hypertension. An inverse correlation between spleen size and platelet count was observed (r = -0.54; P < 0.0001). In patients without splenomegaly, thrombocytopenia was associated with the grade of fibrosis; platelet counts were the highest in patients with fibrosis 0-2, lower in those with grade 3 (P < 0.008) and lowest in those with grade 4 (P < 0.05). These findings were independent of demographic and biochemical characteristics, hepatic necroinflammatory activity, portal hypertension and splenomegaly. Patients with normal platelet counts showed higher thrombopoietin levels than those with low platelet counts (P < 0.0001). An inverse correlation between thrombopoietin levels and fibrosis grade was observed (r = - 0.50; P < 0.0001). Median thrombopoietin levels were 58 and 27 pg/ml for fibrosis grade 0-1 and grade 4 respectively (P < 0.001). These data indicate that advanced hepatic fibrosis, causing an altered production of thrombopoietin and portal hypertension, plays the central role in the pathogenesis of thrombocytopenia in chronic viral hepatitis.     

Eltrombopag in chronic hepatitis C

Chronic hepatitis C is a public health problem worldwide. Unfortunately, not all patients may benefit from antiviral therapy due to thrombocytopenia. Its causes are represented by portal hypertension and platelet sequestration in the spleen, decreased serum levels or activity of thrombopoietin, the bone marrow suppression induced by hepatitis C virus and a possible adverse effect of interferon. Thrombopoietin receptor analogs may contribute to increase platelet counts in these patients. Eltrombopag binds to another region of the thrombopoietin receptor compared to endogenous thrombopoietin and stimulates the proliferation and maturation of megakaryocytes and the platelet production in a dose-dependent manner. Eltrombopag has proven its effectiveness for the treatment of patients with primary immune thrombocytopenia. Its indication for other hemopathies or situations (like thrombocytopenia secondary to chemo- or radiotherapy, acute leukemia, myelodysplastic syndroms, acquired and hereditary bone marrow failure, and platelet donors) is under study. Eltrombopag may be particularly useful in patients with advanced chronic hepatitis or liver cirrhosis who require antiviral treatment. We present a minireview on the results of treatment with eltrombopag in patients chronically infected with hepatitis C virus, highlighting the benefits and mentioning possible adverse effects. In some studies eltrombopag increased the number of virological responses after clasical antiviral treatment of patients with chronic hepatitis C and reduced the transfusional requirements of those who had to be subjected to invasive surgery. Eltrombopag is a solution for many of these patients, which allows them receiving antiviral therapy and sometimes getting a sustained virological response, but they must be well monitored to prevent possible thromboembolic or bone marrow complications or liver failure occurrence.     

Thrombopoietin serum levels are elevated in patients with hepatitis B/C infection compared to other causes of chronic liver disease

BACKGROUND/AIMS: Thrombocytopenia in patients with advanced liver disease may stem from a deficient hepatic thrombopoietin production. METHODS: We determined the relationship between thrombopoietin, thrombocytopenia, aetiology and extent of liver damage by incorporating serum thrombopoietin measurements in the pretransplant evaluation of 111 patients with liver disease. RESULTS: The extent of thrombocytopenia was related to the underlying cause of disease. The platelet count directly correlated with factor V, II, fibrinogen, and PTT, and a negative correlation was found for splenic size and Child's stage. The thrombopoietin concentrations were age-dependent, and no significant difference resulted between the median thrombopoietin level of liver disease patients with age-matched healthy controls. Thrombopoietin concentrations and platelet counts were not correlated. Although noncirrhotic patients had higher platelet counts than those with Child's A-C cirrhosis (p < 0.001, U-test), no such difference was found in thrombopoietin levels. Patients with hepatitis B and/or C had lower platelet counts compared to patients with nonviral diseases (p < 0.001), and their median thrombopoietin concentrations were significantly higher (p < 0.001). CONCLUSION: We conclude that thrombocytopenia in patients with liver disease is unlikely to be explained only based on a deficient hepatic production of thrombopoietin. Patients with chronic viral hepatitis have significantly elevated thrombopoietin levels; the involved pathomechanisms require further study.     

Thrombocytopenia associated with chronic liver disease

Thrombocytopenia (platelet count <150,000/microL) is a common complication in patients with chronic liver disease (CLD) that has been observed in up to 76% of patients. Moderate thrombocytopenia (platelet count, 50,000/microL-75,000/microL) occurs in approximately 13% of patients with cirrhosis. Multiple factors can contribute to the development of thrombocytopenia, including splenic platelet sequestration, bone marrow suppression by chronic hepatitis C infection, and antiviral treatment with interferon-based therapy. Reductions in the level or activity of the hematopoietic growth factor thrombopoietin (TPO) may also play a role. Thrombocytopenia can impact routine care of patients with CLD, potentially postponing or interfering with diagnostic and therapeutic procedures including liver biopsy, antiviral therapy, and medically indicated or elective surgery. Therapeutic options to safely and effectively raise platelet levels could have a significant effect on care of these patients. Several promising novel agents that stimulate TPO and increase platelet levels, such as the oral platelet growth factor eltrombopag, are currently in development for the prevention and/or treatment of thrombocytopenia. The ability to increase platelet levels could significantly reduce the need for platelet transfusions and facilitate the use of interferon-based antiviral therapy and other medically indicated treatments in patients with liver disease.     

病毒性肝炎与糖尿病关系的临床研究

目的探讨病毒性肝炎与糖尿病发病的关系。方法对84例慢性乙型肝炎与83例慢性丙型肝炎患者,76例同期住院患者（对照组）进行病例分析研究,明确其是否合并糖尿病。结果慢性乙型肝炎患者糖尿病并发率为5．9％,慢性丙型肝炎患者糖尿病并发率为13．3％,对照组患者糖尿病并发率为7．9％,慢性丙型肝炎组糖尿病的并发率明显高于慢性乙型肝炎组和对照组患者（P〈0．05）,慢性乙型肝炎组和对照组患者糖尿病并发率差异无统计学意义（P〉0．05）。慢性肝炎合并糖尿病男女比例为2．2：1。三组中合并糖尿病与未合并糖尿病的患者均为中老年人,在年龄、体质量指数、空腹血糖方面差异无统计学意义。合并糖尿病的慢性乙型肝炎和慢性丙型肝炎患者血清丙氨酸氨基转移酶、门冬氨酸氨基转移酶及总胆红素水平高于未合并糖尿病者（P〈0．05）。结论慢性丙型肝炎病毒感染易合并糖尿病,丙型肝炎病毒感染可能是糖尿病的发病因素之一。     

慢性乙型肝炎患者加用益血生胶囊预防α干扰素所致的骨髓抑制

目的：观察α干扰素（IFN-α）治疗慢性乙型肝炎（CHB）时，加用益血生胶囊对防治IFN-α相关性骨髓抑制的作用。方法：105例经肝穿刺活检证实的HBeAg阳性CHB患者，给予IFN-α2b，5MU／次，每周3次，依患者意愿，其中62例加用益血生胶囊口服（试验组），43例未加用（对照组）。以Abbott EIA试剂检测HBeAg，以荧光定量PCR法测定HBV DNA。所有统计学分析均采用意向治疗分析。结果：两组患者性别、年龄、肝组织炎症活动度、肝组织纤维化分期、血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、HBV DNA水平以及治疗前外周血白细胞计数、中性粒细胞计数和血小板计数、IFN-α疗程之间差异均无显著性意义。试验组加用益血生胶囊2．0（1．0～3．2）个月。治疗结束时，试验组、对照组联合应答率分别为42．9％（27／62）和33．3％（14／42）（Х^2=0．960，P=0．327），随访6个月时分别为44．40％（28／62）和33．3％（14／43）（Х^2=1．296，P=0．255）；试验组疗程中白细胞减少（〈4．0×10^9／L）发生率14．5％（9／62）、中性粒细胞减少（〈2．0×10^9／L）发生率19．4％（12／62）、血小板减少（〈100×10^9／L）发生率17．7％（11／62），对照组分别为34．9％（15／43）（Х^2=5．974，P=0．015）、37．2％（16／43）（Х^2=4．139，P=0．042）和41．9％（18／43）（Х^2=7．388，P=0．007）。结论：以IFN-α治疗慢性乙型肝炎时，加用益血生胶囊可减少和减轻IFN-α相关性骨髓抑制。